The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) was measured after intravenous and oral administration to pigs. Eighteen healthy pigs (six for each compound) weighing 22-43 kg received a dose of 10 mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a fasted and a fed condition in a three-way crossover design. The three tetracyclines were present in plasma up to 30 hours after intravenous and after oral administration to fasted as well as fed pigs. The volume of distribution was 1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The bioavailability was in general low for all the three tetracyclines. The presence of food did not affect the bioavailability of OTC, which was only 3% in both fasted and fed pigs. For TC there was a significantly higher bioavailability in fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not significant, being 11% in fasted vs. 6% in fed pigs. Even though the presence of food affected the bioavailability only for TC, it prolonged the absorption phase for all three tetracyclines. Based on the bioavailability and the resulting plasma concentrations, it is concluded that it is not possible to obtain a therapeutically active concentration in plasma or tissues after oral administration of any of the three tetracyclines to fed or fasted pigs.

Experimental porcine nephropathy: Changes of renal function and structure perorally induced by crystalline ochratoxin A. Acta path. microbiol. scand. Sect. A, 84: 429-434, 1976. Nine pigs were fed crystalline ochratoxin A in amounts corresponding to a feed level of 1 mg per kg for 3 months. The only observable lesion developed was a kidney damage, identical to the naturally occurring porcine nephropathy. The changes of renal function was characterized by impairment of proximal tubular function, indicated by a decrease of the ratio ?'mPAH/C,,,, of the ability to concentrate urine, and by an increased urinary excretion of glucose. The decrease of the ratio 1mpAH/CI,, is correlated with time of exposure to ochratoxin A. The changes of renal structure were characterized by degeneration of the proximal tubules, leading to tubular atrophy accompanied by interstitial fibrosis. At the end of the experiment the kidney, liver, adipose and muscular tissue of the slaughtered pigs contained sizable amounts of ochratoxin A residues. As the pigs would have passed the meat inspection this represents a possible health problem. T h e changes observed in this study are identical to those observed by feeding to pigs grains naturally contaminated with ochratoxin A.

The disposition of enrofloxacin was measured after intravenous and oral administration to pigs. Eight clinically healthy pigs weighing 25 to 40 kg received a dose of 5 mg/kg intravenously and 10 mg/kg orally in both a fasted and a fed condition in a three-way cross-over design. Enrofloxacin was present in plasma for up to 72 hr after both intravenous and oral administration to fasted as well as fed pigs. The steady state volume of distribution was determined to 3.950.5 Vkg body weight which indicates that enrofloxacin was widely distributed in the body. The bioavailability was determined to 83213% in fed and to 101?32% in fasted pigs. Based on the bioavailability and the resulting plasma concentrations it is concluded that a therapeutically active concentration for the most common porcine microbial pathogens are maintained for at least 24 hr after oral administration of 10 mg/kg body weight to fasted as well as to fed pigs. Ciprofloxacin which is an active metabolite of enrofloxacin was observed in plasma samples from all treated pigs, but the concentration never exceeded 0.1 pg/ml. During the first 24 hr after the administration of enrofloxacin the concentration of the metabolite made up less than 10% of the corresponding concentration of the parent compound.Bacterial infections, especially in the respiratory and alimentary tract, are very common in pigs and most often have to be treated on a flock basis. Such treatment may include large numbers of pigs, and consequently, the most practical way of dosing the animals is by oral administration of an appropriate antimicrobial agent. Oral administration of drugs to pigs may be done either by mixing the drug with feed, or by dissolving it in the drinking water. In general, the former is preferred because it may be commercially available as medicated feed; not all drugs are watersoluble, and the feed may hide any unpleasant taste of the drug. Mixing of drug and feed may, however, result in interactions affecting the bioavailability of the drug and thereby the possibilities of achieving therapeutically active concentrations at the site of the infection (Palmer et al. 1983;Kniffen et al. 1989). Furthermore, it can be assumed that the influence of feed present in the gastrointestinal tract on the absorption of orally administered drugs will not be the same for different drugs (Yu et al. 1990;Baggot 1992;Sutter et al. 1993). Previous studies with sulphadiazine and trimethoprim (Nielsen & Gyrd-Hansen 1994a) have shown that the bioavailability of these two compounds after oral administration to fasted pigs was 89% and 90%, respectively, versus 85% and 92% in the group of fed pigs. Thus the bioavailability was not significantly influenced by the presence of feed in the gastrointestinal tract. For penicillin V the oral bioavailability was only 19% in fasted and 17% in (Nielsen & Gyrd-Hansen 1994b). In spite of the low bioavailability it was possible to obtain therapeutically active concentrations up to 6 hr after administration of 50 mg/kg body weight to fasted as...

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